GI articles

2021-11-01 - 2021-11-12


This issue includes 229 articles. Please be mindful of the authors and publishers copyright while sharing the content.


Guidelines

Gastroenterology

Updates on Age to Start and Stop Colorectal Cancer Screening: Recommendations From the U.S. Multi-Society Task Force on Colorectal Cancer.

This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age 85.

Gastrointest Endosc

Standardization of EUS imaging and reporting in high-risk individuals of pancreatic adenocarcinoma: consensus statement of the Pancreatic Cancer Early Detection Consortium (PRECEDE).

Adoption of this standardized EUS reporting template should improve consistency in clinical decision making for individuals with elevated risk of pancreatic cancer by providing complete and accurate reporting of pancreatic abnormalities. Standardization will also help to facilitate research and clinical trial design by using clearly defined and consistent imaging descriptions, thus allowing for comparison of results across different centers.

Updates on age to start and stop colorectal cancer screening: recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer.

This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age 85.

Meta-analysis

meta-analyses and systematic reviews

Aliment Pharmacol Ther

Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease.

Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments.

Am J Gastroenterol

Association of Body Mass Index With Risk of Early-Onset Colorectal Cancer: Systematic Review and Meta-Analysis.

Obesity is a strong risk factor for EOCRC, and its increasing prevalence in younger generations is likely to substantially contribute to the increase in EOCRC. Efforts to limit the obesity epidemic in adolescents and younger adults may be crucial for reducing CRC incidence in future generations of adults.

Digital Health Technologies for Remote Monitoring and Management of Inflammatory Bowel Disease: A Systematic Review.

Digital health technologies may be effective in decreasing health care utilization and costs, though may not offer advantage in reducing risk of relapse, QoL, and improving treatment adherence in patients with IBD. These techniques may offer value-based care for population health management.

Meta-Analysis: Placebo Response and Its Determinants in Functional Dyspepsia.

Our systematic review and meta-analysis showed that pooled placebo response rates in double-blinded RCTs of FD depended on efficacy criteria. Trials assessing complete symptom relief showed stable low placebo response rates in short-term trials.

Gut

Bidirectional brain-gut axis effects influence mood and prognosis in IBD: a systematic review and meta-analysis.

Bidirectional effects of the brain-gut axis are present in IBD and may influence both the natural history of the disease and psychological health.

Cross-roads for meta-analysis and network meta-analysis of H. pylori therapy.

90%) for both the study and the comparator regimens. Meta-analyses should be restricted to regimens that meet these criteria and must take into account the presence of marked geographical and host genetic and phenotypic heterogeneity. In addition, to provide clinically relevant results, treatment outcomes should focus on, and present, actual cure rates in addition to odd ratios.

Inflamm Bowel Dis
J Crohns Colitis

Clinical, endoscopic and safety placebo rates in induction and maintenance trials of Crohn's disease: Meta-analysis of Randomised controlled trials.

Placebo remission and response rates in CD trials vary according to the phase of the trial, endpoint assessed and by induction or maintenance design. These contemporary estimates will help to inform future CD trial design.

Systematic Review: Sweet Syndrome Associated with Inflammatory Bowel Disease.

SS may precede or occur with IBD diagnosis in almost one-third of cases. Azathioprine and IBD-associated SS present and behave distinctly, especially with regard to gender, age at diagnosis and recurrence risk. Corticosteroids and TNF-α inhibitors have demonstrated efficacy in treating SS in IBD.

Neurogastroenterol Motil

Oral and parenteral anti-neuropathic agents for the management of pain and discomfort in irritable bowel syndrome: A systematic review and meta-analysis.

Anti-neuropathic analgesics may improve pain in IBS, and deserve further, high-quality investigation, potentially considering parenteral administration and agents with minimal gastrointestinal motility effects. Investigation of amitriptyline's efficacy in non-diarrhea-predominant subtypes is currently lacking, and we recommend particular caution for its use in IBS-C.

Open access

15articles are open access at time of publication, full text is typically available in PMC (link provided). Moreover, many of the guidelines, editorials and case reports are also open access through the provided publisher link.

Am J Gastroenterol

Association of Body Mass Index With Risk of Early-Onset Colorectal Cancer: Systematic Review and Meta-Analysis.

Obesity is a strong risk factor for EOCRC, and its increasing prevalence in younger generations is likely to substantially contribute to the increase in EOCRC. Efforts to limit the obesity epidemic in adolescents and younger adults may be crucial for reducing CRC incidence in future generations of adults.

Identifying Bleeding Etiologies by Endoscopy Affected Outcomes in 10,342 Cases With Hematochezia: CODE BLUE-J Study.

This nationwide data set of acute hematochezia highlights the importance of colonoscopy in accurately detecting bleeding etiologies that stratify patients at high or low risk of adverse outcomes and those who will likely require more procedures. Predicting different bleeding etiologies based on initial presentation would be challenging.
Gastroenterology
Gastrointest Endosc
Hepatology
Inflamm Bowel Dis

Selective Tyrosine Kinase 2 Inhibition for Treatment of Inflammatory Bowel Disease: New Hope on the Rise.

Deucravacitinib, a novel, oral, selective TYK2 inhibitor, and brepocitinib and PF-06826647, TYK2 inhibitors that bind to the active site in the catalytic domain, are in development for IBD and other immune-mediated inflammatory diseases. Allosteric TYK2 inhibition is more selective than JAK1-3 inhibition and has the potential to limit toxicities typically associated with JAK1-3 inhibitors. Future studies will be important in establishing the role of selective, allosteric TYK2 inhibition in the management of IBD.

Randomized Controlled Trial Substudy of Cell-specific Mechanisms of Janus Kinase 1 Inhibition With Upadacitinib in the Crohn's Disease Intestinal Mucosa: Analysis From the CELEST Study.

Upadacitinib modulates inflammatory pathways in mucosal lesions of patients with anti-TNF-refractory Crohn's disease, including inflammatory fibroblast and interferon-γ-expressing cytotoxic T cell compartments. This substudy is the first to describe the molecular response to JAK1 inhibition in inflammatory bowel disease and differential effects relative to anti-TNF treatment. (Clinical trial identifier NCT02365649).
J Crohns Colitis

Suppressing Kv1.3 Ion Channel Activity with a Novel Small Molecule Inhibitor Ameliorates Inflammation in a Humanised Mouse Model of Ulcerative Colitis.

Inhibition of Kv1.3 [by DES1, for instance] appears to be a potential therapeutic intervention strategy for UC patients.

The Impact of Vedolizumab on COVID-19 Outcomes Among Adult IBD Patients in the SECURE-IBD Registry.

COVID-19 outcomes among IBD patients on VDZ are comparable to those on al other therapies. Hospitalization, but not severe COVID-19, is more likely with VDZ monotherapy than with anti-TNF monotherapy. Overall, VDZ appears to be safe in IBD patients with COVID-19.

Histopathological Features in Colonic Biopsies at Diagnosis Predict Long-term Disease Course in Patients with Crohn's Disease.

In this first study investigating the additive predictive value of histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improving stratification and facilitating clinical decision making.

Efficacy and Safety of Tofacitinib Re-treatment for Ulcerative Colitis After Treatment Interruption: Results from the OCTAVE Clinical Trials.

Median time to treatment failure was numerically higher in induction remitters versus induction responders but non-remitters. Following treatment interruption, efficacy was safely and successfully recaptured with tofacitinib 10 mg b.d. re-treatment in a substantial proportion of patients [ClinicalTrials.gov NCT01458574;NCT01470612].

Ustekinumab in Paediatric Patients with Moderately to Severely Active Crohn's Disease: Pharmacokinetics, Safety, and Efficacy Results from UniStar, a Phase 1 Study.

The pharmacokinetics/safety profiles were generally consistent with those observed in adults with Crohn's disease. These results suggest a different dosing regimen may be required for patients <40 kg from that employed in this study; additional pharmacokinetic analyses may be needed in this population.

Effectiveness and Safety of Ustekinumab in Ulcerative Colitis: Real-world Evidence from the ENEIDA Registry.

Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Immunological Networks Defining the Heterogeneity of Inflammatory Bowel Diseases.

We highlight how molecular heterogeneity may relate to clinical phenotype, but in other situations may be independent of clinical phenotype, encouraging future studies to fill the gaps. Finally, we discuss novel stratification methodologies as a foundation for precision medicine, in particular a novel stratification strategy based on conserved genes across species. All of these dimensions of heterogeneity have potential to provide strategies for patient stratification and move IBD practice towards personalised medicine.

Studies

RCT, clinical trials, retrospective studies, etc…

Aliment Pharmacol Ther

Prothrombin induced by vitamin K absence or antagonist-II and alpha foetoprotein to predict development of hepatocellular carcinoma in Caucasian patients with hepatitis C-related cirrhosis treated with direct-acting antiviral agents.

In patients with HCV-related cirrhosis treated with DAA, PIVKA-II and AFP independently predicted HCC, while their combination improved risk stratification.

Am J Gastroenterol

Bristol Stool Scale as a Determinant of Hepatic Encephalopathy Management in Patients With Cirrhosis.

BSS is complementary and additive to BM frequency, can modulate the risk of readmissions and stabilize HE-related therapy changes in outpatients with cirrhosis, and could help personalize HE management.

Chemopreventive Effect of Statin on Hepatocellular Carcinoma in Patients With Nonalcoholic Steatohepatitis Cirrhosis.

Our findings suggest that patients with NASH and bridging fibrosis have a low risk of HCC. Dose-dependent statin use reduced HCC risk significantly in patients with NASH cirrhosis.

Comparison of Cap-Assisted vs Conventional Endoscopic Technique for Management of Food Bolus Impaction in the Esophagus: Results of a Multicenter Randomized Controlled Trial.

This multicenter randomized controlled trial confirmed that the cap-assisted technique is more effective and less costly than the conventional approach and should be first-line treatment for esophageal FBI.

Fasting Ketonuria and the Risk of Incident Nonalcoholic Fatty Liver Disease With and Without Liver Fibrosis in Nondiabetic Adults.

Ketonuria was associated with a reduced risk of developing incident hepatic steatosis with and without intermediate-to-high probability of advanced fibrosis in a large cohort of nondiabetic healthy individuals. The role of hyperketonemia in the prevention of NAFLD requires further exploration.

Feasibility and Accuracy of Artificial Intelligence-Assisted Sponge Cytology for Community-Based Esophageal Squamous Cell Carcinoma Screening in China.

The AI-assisted sponge cytology is feasible, safe, and acceptable for ESCC screening in community, with high accuracy for detecting esophageal squamous high-grade lesions.

Health Economic Impact of a Multicenter Quality-of-Care Initiative for Reducing Unplanned Healthcare Utilization Among Patients With Inflammatory Bowel Disease.

Implementing clinical care process changes using a Collaborative approach was associated with overall cost savings. Future work should examine which specific interventions are most effective and whether such cost savings are sustainable.

Identifying Bleeding Etiologies by Endoscopy Affected Outcomes in 10,342 Cases With Hematochezia: CODE BLUE-J Study.

This nationwide data set of acute hematochezia highlights the importance of colonoscopy in accurately detecting bleeding etiologies that stratify patients at high or low risk of adverse outcomes and those who will likely require more procedures. Predicting different bleeding etiologies based on initial presentation would be challenging.

Long-Term Statin Use, Total Cholesterol Level, and Risk of Colorectal Cancer: A Prospective Cohort Study.

This study does not support benefit of statin use in CRC chemoprevention or any association between total cholesterol level and CRC risk. On the contrary, long-term statin use may be associated with increased colon cancer risk (driven by proximal colon cancer).

Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study.

Second-line therapy with OCA or fibrates improves hepatic biochemistry and the GLOBE score in primary biliary cholangitis patients with suboptimal response to ursodeoxycholic acid. Simultaneous treatment with OCA and fibrates improved ALP as well.

Peppermint Oil Treatment for Irritable Bowel Syndrome: A Randomized Placebo-Controlled Trial.

Peppermint oil and placebo both showed clinically meaningful improvement in IBS symptoms. However, there were no significant differences between the groups. Further large, rigorous trials are needed to evaluate the role of peppermint oil for the treatment of IBS.

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study.

The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.

Targeted Albumin Therapy Does Not Improve Short-Term Outcome in Hyponatremic Patients Hospitalized With Complications of Cirrhosis: Data From the ATTIRE Trial.

Targeted intravenous albumin infusions increased serum sodium level in hospitalized hyponatremic patients with cirrhosis, but this did not improve outcome.

The Results From Up-Front Esophageal Testing Predict Proton Pump Inhibitor Response in Patients With Chronic Cough.

Our results demonstrate the usefulness of an up-front esophageal testing in discriminating reflux-related cough patients and predicting PPI response.

Validity of Secretin Stimulation Testing on Proton Pump Inhibitor Therapy for Diagnosis of Zollinger-Ellison Syndrome.

In our cohort, SSTs on PPI compared with SSTs off PPI were noninferior for sensitivity, specificity, and PPV. These results suggest that PPI withdrawal before SSTs may not be necessary.

Vulvar Crohn's Disease: Clinical Features and Outcomes.

Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases.

Clin Gastroenterol Hepatol

Clinical and Patient Reported Outcomes from Patients with Non-alcoholic Fatty Liver Disease Across the World: Data from the Global NASH/NAFLD Registry.

NAFLD patients seen in real-world practices in different countries experience high comorbidity burden and impaired quality of life. Future research using global data will enable more precise management and treatment strategies for these patients.

Cost-Effectiveness of a Risk-Tailored Pancreatic Cancer Early Detection Strategy Among Patients With New-Onset Diabetes.

A risk-tailored PDAC early detection strategy targeting NoD patients with a minimum predicted 3-year PDAC risk of 1.0% to 2.0% may be cost effective.

Esophageal Dysmotility Is Associated With Disease Severity in Eosinophilic Esophagitis.

Although normal secondary peristalsis was observed frequently in this EoE cohort, abnormal esophageal CRs were related to EoE disease severity, especially features of fibrostenosis. This study evaluating secondary peristalsis in EoE suggests that esophageal wall remodeling, rather than eosinophilic inflammatory intensity, was associated with esophageal dysmotility in EoE.

Sugar-Sweetened Beverage, Diet Soda, and Non-Alcoholic Fatty Liver Disease Over 6 Years: The Framingham Heart Study.

Higher average SSB intake is associated with an increase in liver fat over 6 years of follow-up and an increased odds of incident NAFLD especially among the older cohort whereas no consistent association was observed for the younger Third Generation cohort.

Utility of ultrasound-guided attenuation parameter for grading steatosis with reference to MRI-PDFF in a large cohort.

UGAP has excellent diagnostic accuracy for grading steatosis with reference to MRI-PDFF. Additionally, UGAP has good linearity and negligible bias, suggesting that UGAP has excellent technical performance characteristics that can be widely used in clinical trials and patient care.

Gastroenterology

An integrated taxonomy for monogenic inflammatory bowel disease.

Our taxonomy integrates genetic, clinical and multi-omic data; providing a basis for genomic diagnostics and testable hypotheses for disease functions and treatment responses.

Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease.

Mirikizumab effectively induced endoscopic response after 12 weeks in patients with moderate-to-severe CD and demonstrated durable efficacy to Week 52. A detailed summary can be found in the Video Abstract. ClinicalTrials.gov, Number NCT02589665.

Global prevalence and impact of Rumination syndrome.

The prevalence of rumination syndrome is higher than reported in most previous population studies and is likely underdiagnosed in clinical practice. Awareness of rumination syndrome should be raised among clinicians to improve care for these patients.

Integrative analysis of the Inflammatory Bowel Disease serum metabolome improves our understanding of genetic etiology and points to novel putative therapeutic targets.

An exploratory analysis combining genetics and unbiased serum metabolome surveys can reveal novel biomarkers of disease activity and potential mediators of pathology in IBD.

Off-therapy response after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B: An international, multi-center, multi-ethnic cohort (RETRACT-B study).

The best candidates for NA withdrawal are virally suppressed, HBeAg negative, non-cirrhotic CHB patients with low HBsAg levels, particularly Caucasians with <1000 IU/mL and Asians with <100 IU/mL. However, strict surveillance is recommended to prevent deterioration.

Protective Role of Spermidine in Colitis and Colon Carcinogenesis.

Loss of SMOX is associated with exacerbated colitis and CAC, increased alpha-defensin expression, and dysbiosis of the microbiome. Spd supplementation reverses these phenotypes, indicating that it has potential as an adjunctive treatment for colitis and chemopreventive for colon carcinogenesis.

Randomized controlled-feeding study of dietary emulsifier carboxymethylcellulose reveals detrimental impacts on the gut microbiota and metabolome.

These results support the notion that the broad use of CMC in processed foods may be contributing to increased prevalence of an array of chronic inflammatory diseases by altering the gut microbiome and metabolome.

Gastrointest Endosc

Comparison of endoscopic full-thickness resection and cap-assisted endoscopic full-thickness resection in the treatment of small (≤1.5 cm)gastric gastrointestinal stromal tumors.

EFR-C was found to be the preferable technique for small (≤1.5 cm) gastric GISTs with shorter operation times, lower adverse events, faster postoperative recovery, and shorter hospitalization times as compared with those with EFR.

Evaluation of the visibility of bleeding points using red dichromatic imaging in endoscopic hemostasis for acute GI bleeding (with video).

RDI improves the visibility of bleeding points in AGIB compared with WLI. RDI help endoscopists at al levels of experience to recognize bleeding points, by enhancing the color contrast relative to the surrounding blood.

Long-term clinical outcome after endoscopic resection of esophageal squamous cell carcinoma invading the muscularis mucosae without lymphovascular invasion.

The long-term outcome for patients with pMM ESCC without LVI was favorable after ER; however, this population had a risk of recurrence directly leading to death. Long-term follow-up is necessary, with attention to the timing of recurrence.

Optimizing outcomes for EUS-guided gastroenterostomy; results of a Standardized Clinical Assessment and Management Plan (with video).

The standardized technique used was associated with high technical and clinical success, and low rates of adverse events, morbidity and procedure-related mortality. Adopting a similar uniform systematic approach may improve procedural outcomes and dissemination.

Scissor-type knife precut in balloon enteroscopy-assisted ERCP for patients with difficult biliary cannulation and surgically altered anatomy (with video).

This is the first study to report the use of the SKP technique for difficult biliary cannulation in patients with SAA, which may be serve as a useful option for salvage cannulation during BE-ERCP.

Hepatology

A GLP-1/GLP-2 receptor dual agonist to treat non-alcoholic steatohepatitis: targeting the gut-liver axis and microbiome.

We applied fecal microbiota transplantation (FMT) in order to gain further insight into the mechanism of GLP1/2-Fc-mediated protection. We confirmed that FMT exerted an additive effect on GLP1-Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation and hepatic fibrosis. CONCLUSION: A long-acting dual agonist of GLP-1 and GLP-2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.

Dysregulation of RalA signaling through dual regulatory mechanisms exerts its oncogenic functions in hepatocellular carcinoma.

Our results provide new biological insight that dysregulation of RalA signaling through dual regulatory mechanisms supports its oncogenic functions in HCC. Targeting RalA may serve as a potential alternative therapeutic approach alone or in combination with currently available therapy.

E3 ubiquitin ligase RNF5 protects against hepatic ischemia reperfusion injury by mediating PGAM5 ubiquitination.

We revealed that RNF5 protected against HIR via its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR.

European Liver Transplant Registry: donor and transplant surgery aspects of 16,641 liver transplantations in children.

Pediatric liver transplantation has reached a high efficacy as a cure, or treatment, for severe liver disease in infants and children. Grafts that survived the first year had a half-life time similar to standard human half-life. Transplantation before or after puberty may be the pivot-point for lower long-term outcome in children. Further studies are necessary to re-visit some old concepts regarding transplant benefit (survival time) for small children, the role of recipient pathophysiology versus graft aging, and risk at transition to adult age.

Favorable impact in Hepatitis C related mortality following free-access to direct-acting antivirals in Spain.

These results suggest that the favorable changes in HCV-related mortality observed for Spain after April 2015 are attributable to scaling up free treatment with direct-acting antivirals and reinforce that HCV eradication is on the horizon.

Genetic Variation in the Mitochondrial Glycerol-3-Phosphate Acyltransferase Is Associated With Liver Injury.

Genetic variation in GPAM is associated with susceptibility to liver injury. GPAM may represent a therapeutic target in chronic liver disease.

Global Burden of Non-alcoholic Fatty Liver Disease (NAFLD) and chronic liver disease (CLD) Among Adolescents and Young Adults.

Over the past decade, the causes of CLD among 15-29-year-olds have shifted- viral hepatitis remains the most common cause of CLD deaths but the global burden of HBV incidence is decreasing while NAFLD is the main driver for increased CLD incidence.

IL-6 induced cGGNBP2 encodes a novel protein to promote cell growth and metastasis in intrahepatic cholangiocarcinoma.

Our study demonstrates that cGGNBP2-184aa, a novel protein encoded by IL-6 induced cGGNBP2, formed a positive feedback loop to facilitate ICC progression and may serves as an auxiliary target for clinical IL-6/STAT3-targeting treatments in ICC.

Immunomodulation and RNA interference alter Hepatitis B Virus-specific CD8 T cell recognition of infected HepG2-NTCP.

Immunomodulation, and RNAi, but not nucleos(t)ide analogues, alter recognition of infected HepG2-NTCP by HBV-specific CD8 T cells. Understanding these changes will inform combination treatments for CHB.

Incidence and Prediction of HBsAg Seroconversion in a Prospective Multi-ethnic HBeAg-Negative Chronic Hepatitis B Cohort.

HBsAg loss in predominantly untreated patients with HBeAg-negative chronic hepatitis B can be accurately predicted over a 3-year horizon using a simple validated score (HBRN-SQuARe). This prognostication tool can be used to support patient care and counseling.

Melatonin receptor 1A, but not 1B, knockout decreases biliary damage and liver fibrosis during cholestatic liver injury.

Melatonin ameliorates liver phenotypes through MT1, whereas down-regulation of MT2 promotes liver damage through GPR50/TGFβR1 activation. Blocking GPR50/TGFβR1 binding through modulation of melatonin signaling may be a therapeutic approach for PSC.

Menopausal hormone therapy and risk of biliary tract cancers.

Combination MHT formulations and oral administrations are associated with increased GBC risk, while estrogen-only formulations were associated with a lower cholangiocarcinoma risk. MHT formulation and administration should be carefully considered when prescribing.

SIMPLE Is an Endosomal Regulator That Protects Against NAFLD by Targeting the Lysosomal Degradation of EGFR.

SIMPLE ameliorated NASH by prompting EGFR degradation and can be a potential therapeutic candidate for NASH.

The Serum Proteome and Ursodeoxycholic Acid Response in Primary Biliary Cholangitis.

UDCA under-response in PBC is characterized by elevation of serum chemokines potentially related to cellular senescence and was previously shown to be released by BECs in PBC, suggesting a potential role in the pathogenesis of high-risk disease. These also have potential for development as biomarkers for identification of high-risk disease, and their clinical utility as biomarkers should be evaluated further in prospective studies.

TRIM11 promotes hepatocellular carcinogenesis through ubiquitin-proteasome mediated degradation of PHLPP1.

Our study confirmed that TRIM11 plays an oncogenic role in hepatocellular carcinoma through the PHLPP1/AKT signaling pathway, suggesting that targeting TRIM11 may be a promising target for the treatment of hepatocellular carcinoma.

Inflamm Bowel Dis

A Single Educational Intervention Improves Pregnancy-Related Knowledge and Emotional Health Among Women With IBD Who Are Pregnant or Wish to Conceive.

Uptake of this gastroenterologist-led educational intervention has the potential to improve pregnancy knowledge, promote medication adherence, and enhance quality of life for women with IBD globally.

Anti-TNF-α Treatment Reduces the Baseline Procoagulant Imbalance of Patients With Inflammatory Bowel Diseases.

Patients with IBD have a procoagulant imbalance as shown by increased ETP at baseline. The ETP decreases during treatment with infliximab, which is related to decreased FVIII and FVIII/PC ratio. This effect is also related to the improvement of inflammation as shown by decreased fibrinogen and C-reactive protein.

Clinical Outcomes and Response Predictors of Vedolizumab Induction Treatment for Korean Patients With Inflammatory Bowel Diseases Who Failed Anti-TNF Therapy: A KASID Prospective Multicenter Cohort Study.

Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy.

Colectomy Incidence Rates in Five-Year Data From the Observational Postmarketing Ulcerative Colitis Study of Originator Infliximab.

Colectomy was reported at a higher rate in the IFX group than in the ConvRx group, although patients in the IFX group had more severe disease at baseline and most of the colectomies occurred after patients had been off of IFX for ≥90 days.

Colon Capsule Endoscopy in the Assessment of Mucosal Healing in Crohn's Disease.

The PCC2 shows promise in assessing ileocolonic mucosa, especially in proximal bowel segments, with greater reach of visualization in the small bowel. Given the resource and safety considerations raised by the Coronavirus disease 2019 pandemic, capsule endoscopy has particular significance.This article aims to contribute to the limited body of research surrounding the validity of capsule endoscopy technology in assessing ileocolonic mucosa in Crohn's Disease patients. In doing so, an alternative option for patients enduring frequent endoscopies is given potential.

Combination of Vedolizumab With Tacrolimus Is More Efficient Than Vedolizumab Alone in the Treatment of Experimental Colitis.

Our data show that vedolizumab reduces the number of innate and adaptive immune cells in the mucosa of patients with UC. Further, the combination of vedolizumab with tacrolimus was more efficient to reduce immune cell numbers and to increase therapeutic efficacy than vedolizumab monotreatment. This finding indicates that combination treatment using these two drugs may be beneficial for patients who do not respond to vedolizumab monotherapy.

Current Trends in IBD-Development of Mucosal-Based Biomarkers and a Novel Minimally Invasive Recoverable Sampling System.

A proprietary preservative contained within the chambers of the capsule has been developed to stabilize DNA and proteins for ex vivo microbiome and metabolomics analyses. Surrogate markers such as SPP24 and GUCA2a have been identified to correlate with gut health, intestinal permeability, and inflammation and could be locally sampled by the RSS. The potential clinical utility of an RSS device is broad and would likely be able to guide therapy by allowing for more frequent disease monitoring, aiding in disease characterization, and facilitating in the identification of novel therapeutic targets.

Effects of JAK1-Preferential Inhibitor Filgotinib on Circulating Biomarkers and Whole Blood Genes/Pathways of Patients With Moderately to Severely Active Crohn's Disease.

Several circulating factors with potential as CD activity biomarkers were identified. Larger studies are necessary to investigate the best utility of these markers for CD.

Fecal Amino Acid Analysis in Newly Diagnosed Pediatric Inflammatory Bowel Disease: A Multicenter Case-Control Study.

Fecal amino acids may enhance understanding of the role of host-microbial interactions in the pathophysiology of IBD and may evolve into biomarkers for pediatric IBD diagnostic and personalized medicine.

Hit the Road JAK! The Role of New Oral Treatment in Inflammatory Bowel Disease.

Several other JAK inhibitors are currently being investigated. However, given the wide spectrum of immunosuppressive effects, special attention has been given to the safety profile of these drugs, namely with regard to the occurrence of thromboembolic events, opportunistic infections, and malignancy. In this article, we review key evidence on the efficacy and safety of JAK inhibitors concerning both UC and CD.

International Perspectives on Management of Inflammatory Bowel Disease: Opinion Differences and Similarities Between Patients and Physicians From the IBD GAPPS Survey.

Patients could benefit from education about disease remission and expectations for current therapies. High corticosteroid use is concerning to patients, and physicians should minimize the use of corticosteroids for extended periods of time.

Neutrophil Extracellular Trap Density Increases With Increasing Histopathological Severity of Crohn's Disease.

These data indicate an association between increased NET formation and CD severity, potentially due to excessive MPO-mediated HOCl production in the extracellular domain, causing host tissue damage that exacerbates CD.

Nonhypoalbuminemic Inflammatory Bowel Disease in Dogs as Disease Model.

Our data described dysregulated immune responses in dogs affected by IBD without protein loss. Despite fairly homogeneous dog cohorts, we were still faced with interindividual variability, and new studies with larger cohorts are needed to validate the dog as a model.

Novel Genetic Variant Predicts Surgical Recurrence Risk in Crohn's Disease Patients.

Novel genetic locus rs2060886 in TCF4 was associated with surgical recurrence risk at genome-wide significance level among CD patients after their first abdominal surgery. Early era of CD first intestinal surgery predicts higher surgical recurrence risk. These results suggest that genetic variants may help guide the CD management strategy in patients at the highest risk of repeated abdominal surgeries.

Outcome of Reverse Switching From CT-P13 to Originator Infliximab in Patients With Inflammatory Bowel Disease.

Reverse switching occurred in 9.9% of patients, predominantly for biosimilar-attributed adverse effects. Switching back to originator infliximab seems effective in patients who experience adverse effects, worsening gastrointestinal symptoms, or loss of response after switching from originator infliximab to CT-P13.

PAR-1 Antagonism to Promote Gut Mucosa Healing in Crohn's Disease Patients: A New Avenue for CVT120165.

This review gathers the scientific evidences of a potential role for PAR-1 in mucosal damage and mucosal dysfunctions associated with chronic intestinal inflammation. The potential clinical benefits of PAR-1 antagonism to promote mucosal repair in CD patients are discussed. Targeted local delivery of a PAR-1 antagonist molecule such as CVT120165, a formulated version of the FDA-approved PAR-1 antagonist vorapaxar, at the mucosa of Crohn's disease patients could be proposed as a new indication for IBD that could be rapidly tested in clinical trials.

Phenotype and Natural History of Children With Coexistent Inflammatory Bowel Disease and Celiac Disease.

Children with IBD and CeD may have peculiar features with a higher risk for autoimmune diseases, colectomy, and pubertal delay compared with IBD alone.

RAID Prediction: Pilot Study of Fecal Microbial Signature With Capacity to Predict Response to Anti-TNF Treatment.

A specific bacterial signature could beneficiate patients with inflammatory bowel disease predicting the therapeutic effectiveness of an anti-TNF treatment, leading to a personalized therapy, improving the patients' quality of life, saving costs and gaining time in patient improvement.

Randomized Controlled Trial Substudy of Cell-specific Mechanisms of Janus Kinase 1 Inhibition With Upadacitinib in the Crohn's Disease Intestinal Mucosa: Analysis From the CELEST Study.

Upadacitinib modulates inflammatory pathways in mucosal lesions of patients with anti-TNF-refractory Crohn's disease, including inflammatory fibroblast and interferon-γ-expressing cytotoxic T cell compartments. This substudy is the first to describe the molecular response to JAK1 inhibition in inflammatory bowel disease and differential effects relative to anti-TNF treatment. (Clinical trial identifier NCT02365649).

Regional Gray Matter Volume Changes in Brains of Patients With Ulcerative Colitis.

The current neuroimaging findings were involved in visceral sensory pathways and were partially associated with the levels of anxiety and depression and clinical stage of patients with UC. This study might provide evidence for possible neuromechanisms of UC.

Research-Based Product Innovation to Address Critical Unmet Needs of Patients with Inflammatory Bowel Diseases.

This special IBD Innovate® supplement is a collection of articles reflecting the diverse and exciting research and development that is currently ongoing in the inflammatory bowel disease field to deliver innovative and differentiated products addressing critical unmet needs of patients. Here, we highlight the pipeline of new product opportunities currently advancing at the preclinical and early clinical development stages. We categorize and describe novel and differentiated potential product opportunities based on their potential to address the following critical unmet patient needs: (1) biomarkers for prognosis of disease course and prediction/monitoring of treatment response; (2) restoration of eubiosis; (3) restoration of barrier function and mucosal healing; (4) more effective and safer anti-inflammatories; (5) neuromodulatory and behavioral therapies; (6) management of disease complications; and (7) targeted drug delivery.

Site- and Taxa-Specific Disease-Associated Oral Microbial Structures Distinguish Inflammatory Bowel Diseases.

Collectively, these data indicate the potential of using oral microbial profiles in screening and monitoring patients with IBD. Furthermore, these results support the importance of spatial and longitudinal microbiome sampling to interpret disease-associated dysbiotic states and eventually to gain insights into disease pathogenesis.

Success of Cyclosporin and Tofacitinib Combination Therapy in a Patient With Severe Steroid-refractory Ulcerative Colitis.

At present, the conventional therapies for acute severe ulcerative colitis (ASUC) mainly include corticosteroids, cyclosporin, and biological agents. However, the treatment of patients with severe steroid-refractory ulcerative colitis remains a serious challenge to clinicians. This study reports a case of steroid-refractory ASUC treated with cyclosporin combined with tofacitinib after treatment failure with infliximab.

Target-Based Small Molecule Drug Discovery Towards Novel Therapeutics for Inflammatory Bowel Diseases.

We will also discuss emerging evidence of a distinct mechanism of action, bromodomain-containing protein 4, an epigenetic regulator of pathways involved in the activation, communication, and trafficking of immune cells. We highlight their chemotypes, mode of actions, structure-activity relationships, characterizations, and their in vitro/in vivo activities and therapeutic potential. The perspectives on the relevant challenges, new opportunities, and future directions in this field are also discussed.

Trajectories of Fatigue in Inflammatory Bowel Disease.

The results clearly showed the existence of distinct fatigue paths over time in patients with IBD. Those reporting more chronic elevated levels of fatigue also reported greater disease activity and reduced well-being. Therefore, reducing disease activity may be important for the treatment of fatigue. In addition, given the significant association with well-being, it is possible that reducing fatigue may improve self-reported well-being.

Translating Results from VARSITY to Real World: Adalimumab vs Vedolizumab as First-line Biological in Moderate to Severe IBD.

This real-world cohort study of biologic-naïve IBD patients found VDZ to be superior to ADM as first-line treatment for patients with UC-but not CD-regarding endoscopic remission at week 52 and treatment persistence.

J Crohns Colitis

A Phase II, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability and Efficacy of Amiselimod in Patients with Moderate to Severe Active Crohn's Disease.

Amiselimod 0.4 mg for 12 weeks was not superior to placebo for the induction of clinical response (CDAI 100) in Crohn's disease. Treatment with amiselimod 0.4 mg was generally well tolerated and no new safety concerns related to amiselimod were reported in this study.

Acceptance and Perceived Control are Independently Associated With Quality of Life in Inflammatory Bowel Disease: Introduction of a New Segmentation Model.

The segmentation model based on disease acceptance and perceived control is valid in IBD patients and discriminates different segments that correlate independently with quality of life. This may open new strategies for patient care.

Association Between Inflammatory Bowel Disease and Psychiatric Morbidity and Suicide: A Swedish Nationwide Population-Based Cohort Study With Sibling Comparisons.

Adult-onset IBD was associated with an increased risk of psychiatric disorders and suicide attempts. Psychological follow-up should be provided to patients with IBD, especially those with extraintestinal manifestations and elderly-onset IBD. This follow-up should be within the first year after IBD diagnosis.

Crohn's disease and early exposure to thiopurines are independent risk factors for mosaic chromosomal alterations in patients with inflammatory bowel diseases.

The difference in mCAs between patients with CD and UC supports the higher incidence of hematopoietic malignancies in CD. Caution should be exercised when using thiopurines in young patients with IBD, particularly CD, in light of possible chromosomal alterations.

Depression and Inflammatory Bowel Disease: A Bidirectional two-sample Mendelian Randomization Study.

Our findings corroborated a causal association of depression on IBD, which may impact the clinical decision on the management of depression in patients with IBD. Though our results did not support a causal effect of IBD on depression, further investigations are needed to clarify the effect of IBD activity on depression (with different symptomology).

Effectiveness and Safety of Ustekinumab in Ulcerative Colitis: Real-world Evidence from the ENEIDA Registry.

Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Efficacy and Outcomes of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease.

Based on the findings from this large US multi-center cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.

Efficacy and Safety of Tofacitinib Re-treatment for Ulcerative Colitis After Treatment Interruption: Results from the OCTAVE Clinical Trials.

Median time to treatment failure was numerically higher in induction remitters versus induction responders but non-remitters. Following treatment interruption, efficacy was safely and successfully recaptured with tofacitinib 10 mg b.d. re-treatment in a substantial proportion of patients [ClinicalTrials.gov NCT01458574;NCT01470612].

Histopathological Features in Colonic Biopsies at Diagnosis Predict Long-term Disease Course in Patients with Crohn's Disease.

In this first study investigating the additive predictive value of histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improving stratification and facilitating clinical decision making.

Identification of Three Novel Susceptibility Loci for Inflammatory Bowel Disease in Koreans in an Extended Genome-Wide Association Study.

The identification of novel loci not previously associated with IBD suggests the importance of studying IBD genetics in diverse populations.

Improving care for recently diagnosed inflammatory bowel disease patients: Lessons learned from a patient-centred, mixed-method study.

In this study, the SATI-Q questionnaire was developed and validated to assess patient satisfaction with care in early IBD. Our findings suggest that psychosocial care and information on IBD medication, diet influence and future perspectives for recently diagnosed IBD patients require improvement.

Obesity in Inflammatory Bowel Disease Is Associated with Early Readmissions Characterised by an Increased Systems and Patient-level Burden.

Obesity in IBD appears to be associated with increased early readmission, characterised by a higher burden, despite the introduction of weight-based therapeutics. Prevention of obesity should be a focus in the treatment of IBD to decrease readmission and health care burden.

Oral CBD-rich Cannabis Induces Clinical but Not Endoscopic Response in Patients with Crohn's Disease, a Randomised Controlled Trial.

Eight weeks of CBD-rich cannabis treatment induced significant clinical and QOL improvement without significant changes in inflammatory parameters or endoscopic scores. The oral CBD-rich cannabis extract was well absorbed. Until further studies are available, cannabis treatment in Crohn's disease should be used only in the context of clinical trials.

Outcomes and long-term effects of COVID-19 in patients with inflammatory bowel diseases - a Danish prospective population-based cohort study with individual-level data.

In this population-based study of 516 patients with IBD and COVID-19, 13.6% needed hospitalization and 2.1% required intensive care. Furthermore, sequelae were frequent affecting 43.7% of COVID-19 infected. These findings might have implications for planning the healthcare of patients in the post-COVID-19 era.

Personalized Medicine with IL-23 Blockers: Myth or Reality?

IL-23 antagonism is a promising therapeutic approach in IBD. Further exploration of molecular and clinical predictors of response may identify patients most likely to benefit from these medications.

Prevalence and Impact of Obesity on Disease-specific Outcomes in a Population-based Cohort of Patients with Ulcerative Colitis.

The prevalence of obesity in the UC population is increasing and may have negative prognostic implications, specifically regarding risk of future hospitalisation and corticosteroid use. Additional prospective studies are necessary to more clearly define these associations.

Rectal Cancer Incidence is Low Following Rectal Diversion or Subtotal Colectomy for IBD: Results of a Population-based Study.

Among patients with a retained rectum following surgery for IBD, the risk of rectal cancer is low and appears to be lower when surveillance endoscopy is performed. Expectant management with surveillance endoscopy may be a reasonable alternative to completion proctectomy in selected patients.

Suppressing Kv1.3 Ion Channel Activity with a Novel Small Molecule Inhibitor Ameliorates Inflammation in a Humanised Mouse Model of Ulcerative Colitis.

Inhibition of Kv1.3 [by DES1, for instance] appears to be a potential therapeutic intervention strategy for UC patients.

The Impact of Vedolizumab on COVID-19 Outcomes Among Adult IBD Patients in the SECURE-IBD Registry.

COVID-19 outcomes among IBD patients on VDZ are comparable to those on al other therapies. Hospitalization, but not severe COVID-19, is more likely with VDZ monotherapy than with anti-TNF monotherapy. Overall, VDZ appears to be safe in IBD patients with COVID-19.

Ustekinuma b for Crohn's Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study.

After 104 weeks of ustekinumab treatment, one-third of CD patients were in corticosteroid-free clinical remission.

Ustekinumab in Paediatric Patients with Moderately to Severely Active Crohn's Disease: Pharmacokinetics, Safety, and Efficacy Results from UniStar, a Phase 1 Study.

The pharmacokinetics/safety profiles were generally consistent with those observed in adults with Crohn's disease. These results suggest a different dosing regimen may be required for patients <40 kg from that employed in this study; additional pharmacokinetic analyses may be needed in this population.

Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation.

Overall, we describe a novel genetic syndrome and identify a critical role for STXBP3 in VEOIBD, sensorineural hearing loss and immune dysregulation.

J Hepatol

A simple clinical score to promote and enhance ferroportin disease screening.

We describe a readily available score with definite criteria and good diagnosis performance that could help screening patients for Ferroportin disease in routine clinical practice.

EDP-305 in patients with NASH: A phase II double-blind placebo-controlled dose-ranging study.

EDP-305 reduced ALT levels and MRI-PDFF supporting development of EDP-305 in patients with NASH in a longer-term trial assessing liver histology.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

The national MELD≥30 priority allocation was associated with improved patient outcomes, although MELD≥30 had a higher risk of graft loss. The transplant centers volume and competition among centers may have a role in the recipient prioritization and outcome. Clinical trial number NCT04530240

Membrane-delimited signaling and cytosolic action of MG53 preserve hepatocyte integrity during drug-induced liver injury.

Our data show that the membrane-delimited signaling and cytosolic dual action of MG53 effectively preserves hepatocyte integrity during DILI. rhMG53 may be a potential treatment option for patients with DILI.

SEBELIPASE ALFA IN CHILDREN AND ADULTS WITH LYSOSOMAL ACID LIPASE DEFICIENCY: FINAL RESULTS OF THE ARISE STUDY.

Early and rapid improvements in markers of liver injury and lipid abnormalities with sebelipase alfa were sustained, with no progression of liver disease, for up to 5 years.

Neurogastroenterol Motil

Reversal of the effects of focal suppression on pharyngeal corticobulbar tracts by chemesthesis coupled with repeated swallowing.

We conclude that interventional paradigms with CW have the capacity to reverse the effects of a focal suppression with 1Hz rTMS more strongly than non-CW or saliva swallowing alone, producing site specific bi-hemispheric changes in corticopharyngeal excitability. Our data suggest that carbonation produces the effects through a mainly cortical mechanism.

Reviews/Editorials

Plenty of the editorials have full text available through the publisher website using the provided link

Aliment Pharmacol Ther
Am J Gastroenterol

Statins and Liver Cancer in Cirrhosis: The Most Relevant Questions Are Still Unanswered.

Abstract Several observational studies have shown an association between statin use and lower incidence of liver cancer. However, several potential biases limit a causal interpretation that could lead to a recommendation of statin prescription to patients with cirrhosis in the absence of a cardiovascular indication. Ongoing randomized trials will soon provide a clearer picture on the efficacy and safety of statins for preventing liver cancer and other complications of cirrhosis.

Clin Gastroenterol Hepatol
Gastroenterology
Inflamm Bowel Dis

Selective Tyrosine Kinase 2 Inhibition for Treatment of Inflammatory Bowel Disease: New Hope on the Rise.

Deucravacitinib, a novel, oral, selective TYK2 inhibitor, and brepocitinib and PF-06826647, TYK2 inhibitors that bind to the active site in the catalytic domain, are in development for IBD and other immune-mediated inflammatory diseases. Allosteric TYK2 inhibition is more selective than JAK1-3 inhibition and has the potential to limit toxicities typically associated with JAK1-3 inhibitors. Future studies will be important in establishing the role of selective, allosteric TYK2 inhibition in the management of IBD.

J Crohns Colitis

Immunological Networks Defining the Heterogeneity of Inflammatory Bowel Diseases.

We highlight how molecular heterogeneity may relate to clinical phenotype, but in other situations may be independent of clinical phenotype, encouraging future studies to fill the gaps. Finally, we discuss novel stratification methodologies as a foundation for precision medicine, in particular a novel stratification strategy based on conserved genes across species. All of these dimensions of heterogeneity have potential to provide strategies for patient stratification and move IBD practice towards personalised medicine.

Neurogastroenterol Motil

Bile Acid Diarrhea in Adults and Adolescents.

These assays are widely available through reference laboratories, and they are being simplified (eg, measurement of primary fecal bile acids in a random stool sample). BAD has also been identified as a co-factor contributing to persistent diarrhea in other diseases in remission including inflammatory bowel disease, microscopic colitis, celiac disease, and neuroendocrine tumors. In summary, advances in diagnosis of BAD provide opportunities for generalists and pediatric and adult gastroenterologists to provide targeted treatment for BAD presenting as chronic non-bloody diarrhea.

Letters&Replies

Letters to the editors and authors’ replies

Aliment Pharmacol Ther
Am J Gastroenterol
Clin Gastroenterol Hepatol
Gastroenterology
Gastrointest Endosc
Gut
Hepatology

Letter to the Editor: standardization of HBV RNA assay for the different phases of chronic hepatitis B is essential.

We read with interest the article by Mak et al (1) that assessed HBV-RNA profiles using real-time PCR (m2000 system, Abbott Diagnostics, Abbott Park, USA), and their correlation with other viral biomarkers, in a large cohort of chronic hepatitis-B (CHB) patients, either treatment-naïve or receiving nucleos(t)ide analogues. The authors reported median serum levels of HBV-DNA higher than HBV-RNA by 1-2 log in both HBeAg-positive and HBeAg-negative treatment-naïve patients.

J Hepatol

Others

all remaining publications eg case reports, images of the month, etc…

Am J Gastroenterol
Clin Gastroenterol Hepatol
Gastroenterology
Gastrointest Endosc
Gut
Hepatology
Inflamm Bowel Dis
J Crohns Colitis
J Hepatol